Endometriosis Is a Cause of Infertility. Does Reactive Oxygen Damage to Gametes and Embryos Play a Key Role in the Pathogenesis of Infertility Caused by Endometriosis?

Abstract

Approximately, 10–15% of women of reproductive age are affected by endometriosis, which often leads to infertility. Endometriosis often has an inherited component, and several causative predisposing factors are hypothesized to underlie the pathogenesis of endometriosis. One working hypothesis is the theory of retrograde menstruation. According to the theory of retrograde menstruation, components of refluxed blood, including apoptotic endometrial tissue, desquamated menstrual cells, lysed erythrocytes, and released iron, induce inflammation in the peritoneal cavity. This in turn activates macrophage release of reactive oxygen species (ROS), leading to oxidative stress via the respiratory burst. Refluxed blood promotes the Fenton reaction, terminating in the production of hydroxyl radical, the most potently destructive ROS. In this article, we review the papers that demonstrate decreased quantity and quality of oocytes and embryos retrieved from IVF/ICSI patients with endometriosis. We discuss literature data demonstrating that ROS are generated in endometriotic tissues that have physical proximity to gametes and embryos, and demonstrating adverse impacts on oocyte, sperm and embryo microtubule apparatus, chromosomes, and DNA. Data that addresses the notions that endometriosis causes oocyte and fetal aneuploidy and that these events are mediated by ROS species are also discussed. Literature data are also discussed that employ use of anti-oxidant molecules to evaluate the importance of ROS-mediated oxidative damage in the pathogenesis of endometriosis. Studies are discussed that have employed anti-oxidants compounds as therapeutics to improve oocyte and embryo quality in infertile subjects, and improve fertility in patients with endometriosis.

Mast Cells in Peritoneal Fluid From Women With Endometriosis and Their Possible Role in Modulating Sperm Function

“…Population-based studies estimate a prevalence ranging between 1.8 and 3.3% in women aged 15-50 years (Morassutto et al, 2016). Endometriosis is frequently associated with infertility, even if affected women have an ovulatory activity or a mechanical patency of the fallopian tubes (Gupta et al, 2008;Máté et al, 2018).…”

The Outcomes of Invitro Fertilization and Embryo Transfer in Endometriosis-Associated Infertility: A Case Control Study

“…The result is the release of cytokines and growth factors (IL-1.6 and IL-8, TNF, RANTES, VEGF) and subsequently spur angiogenesis around implants. With the formation of new capillaries around the lesion, endometriosis cells can proliferate well [11].…”

“…Increased number of inflammatory cells in the peritoneal fluid but has also been shown to have toxic effects on the embryo. The increase in free radicals in the enometrium as shown by the increased expression of glutathione peroxidase and catalase also has a negative impact on embryonic development [9,11].…”

“…In patients with endometriosis integrin expression decreases so that it can cause interference with embryo implantation.There is a correlation between the effects of embryonic fluid peritoneal and serum of endometriosis patients. This suggested that embryotoxic factors enter and circulate in the systemic circulation and affect early embryogenesis in the reproductive organs [11,12]. In endometriosis,the level of IgG and IgA antibodies to endometrial antigen and lymphocytes are increase.…”

“…Autoantibodies to endometrial antigens increase in women with endometriosis. Endometriosis is associated with recurrent abortion and possible infertility due to abnormal autoantibodies [11].…”